The CLL Research Consortium (CRC) is multi-institutional research program with a mission to develop improved and potentially curative treatments for patients with chronic lymphocytic leukemia (CLL). The CRC provides an infrastructure that facilitates research on novel therapies and on clinical-laboratory relationships that improve clinical staging and/or assist in the early assessment of response to therapy. The CRC has six projects. Proj, 1 (Croce) investigates the genetic basis for CLL and examines the expression and function of non-coding RNA found to influence pathogenesis and disease progression. Proj, 2 (Reed) examines novel chemical antagonists that target proteins that inhibit apoptosis. Proj, 3 (Kipps) examines strategies for active immune therapy, factors involved in the cross talk in the CLL-cell microenvironment, and novel approaches to target R0R1, a leukemia-associated antigen. Proj. 4 (Gribben) evaluates T cell defects that impair cognate intercellular interactions and/or development of effective anti-tumor immunity and investigates strategies for allogeneic stem cell transplantation. Proj. 5 (Plunkett) examines the activity of promising anticancer agents alone or in mechanism-based combinations. Proj. 6 (Grever) studies inhibitors of key metabolic pathways implicated in pathogenesis and/or disease progression. The CRC has 4 cores: Core A (Kipps) provides scientific and administrative oversight, organizes meetings, facilitates communication, monitors for compliance with regulatory agencies, and provides biomedical informatics and data management. Core B (Neuberg) assists in the design, implementation, and data analyses of basic and clinical research projects. Core C (Rassenti) provides for tissue banking, sample trafficking, and sample validation. It ensures uniform analyses of genetic and phenotypic features of stored samples, processes samples from patients treated on CRC clinical studies, and ensures appropriate access to samples for correlative science studies and hypothesis-testing research. Core D (Wierda) facilitates development and execution of clinical trials, identifies new strategies for treatment, facilitates correlative laboratory studies, and assesses laboratory and clinical parameters collected on patients participating in CRC clinical studies.